[Note: According to an accompanying editorial on this placebo-controlled study, “SAMe offers a novel mechanism of treatment action and opens up a new area for future exploration.” And, while questions must be addressed in further studies, “demonstration of a new treatment for depression with a novel mechanism is exciting news.”]

Objective: Despite the progressive increase in the number of antidepressants, many patients with major depressive disorder continue to be symptomatic. Clearly, there is an urgent need to develop better tolerated and more effective treatments for this disorder.

The use of S-adenosyl methionine (SAMe) - a naturally occurring molecule that serves as a methyl donor in human cellular metabolism - as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development.

Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial.

The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale (HAM-D).

Results: The HAM-D response and remission rates were higher for patients treated with adjunctive SAMe (36.1% and 25.8%, respectively) than adjunctive placebo (17.6% versus 11.7%, respectively). The number needed to treat for response and remission was approximately one in six and one in seven, respectively.

There was no statistically significant difference in the proportion of SAMe- versus placebo-treated patients who discontinued the trial for any reason (20.6% versus 29.5%, respectively), due to adverse events (5.1% versus 8.8%, respectively), or due to inefficacy (5.1% versus 11.7%, respectively).

Conclusions: These preliminary results suggest that SAMe can be an effective, well-tolerated, and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication.